Recent advancements in metal-catalyst-free multicomponent radical sulfonylation of alkynes.

Vinyl sulfones are crucial building blocks in synthetic chemistry and core structural units of pharmaceutically active molecules, thus extensive investigations have been conducted on the construction of these skeletons. In contrast to the classical synthetic approaches, the radical sulfonylation of alkynes for producing vinyl sulfones has garnered considerable interest because of its mild conditions and high efficiency. Radical sulfonation of alkynes typically begins with the sulfonyl radical attacking the alkynes, followed by further functionalization. Moreover, the association of metal-catalyst-free systems with multicomponent reactions (MCRs) offers an environmentally friendly pathway for efficiently constructing complex scaffolds from readily available partners. However, there is no comprehensive review summarizing the advancements in metal-catalyst-free multicomponent radical sulfonylation of alkynes. Hence, we provide a categorical overview based on the objects of sulfonylation of alkynes (hydrosulfonylation, carbosulfonylation, aminosulfonylation, oxysulfonylation, sulfosulfonylation, selenosulfonylation, and iodosulfonylation), along with interpretations of the reaction mechanisms.

The discovery of a novel single-function intermolecular Diels-Alder enzyme for the biosynthesis of hetero-dimer lithocarpins.

The deep-sea fungus Phomopsis lithocarpus FS508 produces tenellone-macrolide conjugated hetero-dimer lithocarpins A-G with anti-tumor activities. The deficiency of new intermolecular Diels-Alder (DA) enzymes hindered the development of new bioactive hetero-dimers. A novel single-function intermolecular DA enzyme, g7882, was initially discovered in this study. The deletion of g7882 led to the disappearance of lithocarpin A and an increase in precursor level . the overexpression of g7882 significantly improved lithocarpin A yield. The in vitro function of g7882DA was also confirmed by biochemical reaction using tenellone B as a substrate. Additionally, the knockout of KS modules of PKS in cluster 41 and cluster 81 (lit cluster) eliminated the production of lithocarpins, which firstly explains the biosynthetic process of hetero-dimer lithocarpins mediated by DA enzyme in FS508. Furthermore, the removal of a novel acetyltransferase GPAT in cluster 41 and the oxidoreductase, prenyltransferase in cluster81 resulted in the reduction of lithocarpin A in P. lithocarpus. The overexpression of gpat in P. lithocarpus FS508 improved the yield of lithocarpin A significantly and produced a new tenellone derivative lithocarol G. This study offers a new DA enzyme tool for the biosynthesis of novel hetero-dimer and biochemical clues for the biosynthetic logic elucidation of lithocarpins.

Energy Transfer-Dominated Quasi-2D Blue Perovskite Light-Emitting Diodes.

The bromide-chloride mixed quasi-two-dimensional (2D) perovskite, with a natural quantum well structure and tunable exciton binding energy, has gained significant attention for high-performance blue perovskite light-emitting diodes (PeLEDs). However, the relative importance of having a low trap state density or efficient exciton transfer for high-efficiency electroluminescence (EL) performance remains elusive. Here, two molecules with the benzoic acid group, sodium 4-fluorobenzoate (SFB) and 3,5-dibromobenzoic acid (DBA), are used to modulate the phase distribution and trap state to explore the effect between energy transfer and defect passivation. As a result, when the n = 1 phase is inhibited in both films, the DBA@SFB-modified perovskite films achieve a higher photoluminescence quantum yield (PLQY) than the SFB-modified perovskite films due to effective defect passivation. However, DBA@SFB-modified PeLEDs exhibit lower external quantum efficiency (EQE) compared to SFB-modified PeLEDs due to the poor exciton transfer between the low-dimensional phase. This demonstrates that passivation strategies may enhance photoluminescence through reducing nonradiative recombination, but the effect of phase distribution is pivotal for EL performance by efficient energy transfer in quasi-2D perovskites. Femtosecond time-resolved transient absorption measurements confirm the fastest carrier dynamics in SFB-modified perovskite films, further corroborating the above result. This work provides useful information about phase modulation and defect passivation for high-efficiency blue quasi-2D PeLEDs.

Manganese(I)-catalyzed nucleophilic addition of C(sp3)-H bonds to aldehydes.

The C-H bond activation catalyzed by a manganese(I) complex has achieved significant development but is limited to C(sp2)-H bonds. In this work, an efficient manganese(I)-catalyzed direct nucleophilic addition reaction of C(sp3)-H bonds to aromatic aldehydes has been developed. This is the first example of manganese(I)-catalyzed C(sp3)-H bond transformation. A manganacycle complex was isolated and proved to be the key active intermediate in the catalytic cycle.

Pararorine A, isoindolinone alkaloid from the endophytic fungus Paramyrothecium roridum and its anti-tumor activity.

Pararorine A, a new isoindolinone alkaloid was isolated from Paramyrothecium roridum, an endophytic fungus from the medicinal plant Gynochthodes officinalis (F.C. How) Razafim. & B. Bremer. The structure of this compound was elucidated by extensive spectroscopic (UV, IR, MS, and NMR) analyses. In addition, the antitumor activity of pararorine A was evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that pararorine A exhibited potent antitumor activities with the IC50 values ranging from 1.69 to 8.95 µM. Moreover, the tumor cell inhibitory activity of pararorine A was evidenced by promoting cytochrome C release and cell cycle arrest as well as the induction of apoptosis by the up-regulation of the protein expressions of JNK and Bax through PARP-cleavage and caspase 3-cleavage.

Irpexols A-C, xanthone derivatives from the endophyte fungus Irpex laceratus A878.

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly­oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 µM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 µM.

Cohort profile: the China surgery and anesthesia cohort (CSAC).

The China Surgery and Anaesthesia Cohort (CSAC) study was launched in July 2020 and is an ongoing prospective cohort study recruiting patients aged 40-65 years who underwent elective surgeries with general anaesthesia across four medical centres in China. The general objective of the CSAC study is to improve our understanding of the complex interaction between environmental and genetic components as well as to determine their effects on a wide range of interested surgery/anaesthesia-related outcomes. To achieve this goal, we collected enriched phenotypic data, e.g., sociodemographic characteristics, lifestyle factors, perioperative neuropsychological changes, anaesthesia- and surgery-related complications, and medical conditions, at recruitment, as well as through both active (at 1, 3, 7 days and 1, 3, 6, 12 months after surgery) and passive (for more than 1 year after surgery) follow-up assessments. We also obtained omics data from blood samples. In addition, COVID-19-related information was collected from all participants since January 2023, immediately after COVID-19 restrictions were eased in China. As of July 18, 2023, 12,766 participants (mean age = 52.40 years, 57.93% were female) completed baseline data collection (response rate = 94.68%), among which approximately 70% donated blood and hair samples. The follow-up rates within 12 months after surgery were > 92%. Our initial analyses have demonstrated the incidence of and risk factors for chronic postsurgical pain (CPSP) and postoperative cognitive dysfunction (POCD) among middle-aged Chinese individuals, which may prompt further mechanistic exploration and facilitate the development of effective interventions for preventing those conditions. Additional studies, such as genome-wide association analyses for identifying the genetic determinants of CPSP and POCD, are ongoing, and their findings will be released in the future.

Rosemary: Unrevealing an old aromatic crop as a new source of promising functional food additive-A review.

Rosemary (Rosmarinus officinalis L.) is one of the most famous spice plants belonging to the Lamiaceae family as a remarkably beautiful horticultural plant and economically agricultural crop. The essential oil of rosemary has been enthusiastically welcome in the whole world for hundreds of years. Now, it is wildly prevailing as a promising functional food additive for human health. More importantly, due to its significant aroma, food, and nutritional value, rosemary also plays an essential role in the food/feed additive and food packaging industries. Modern industrial development and fundamental scientific research have extensively revealed its unique phytochemical constituents with biologically meaningful activities, which closely related to diverse human health functions. In this review, we provide a comprehensively systematic perspective on rosemary by summarizing the structures of various pharmacological and nutritional components, biologically functional activities and their molecular regulatory networks required in food developments, and the recent advances in their applications in the food industry. Finally, the temporary limitations and future research trends regarding the development of rosemary components are also discussed and prospected. Hence, the review covering the fundamental research advances and developing prospects of rosemary is a desirable demand to facilitate their better understanding, and it will also serve as a reference to provide many insights for the future promotion of the research and development of functional foods related to rosemary.

A new secondary metabolite from the marine-derived fungus Phomopsis lithocarpus FS508.

Based on the One Strain-Many Compounds (OSMAC) strategy, the secondary metabolites of Phomopsis lithocarpus FS508 were investigated. As a result, a new secondary metabolite, 4-methoxy-3-[4-(acetyloxy)-3-methyl-2-butenyl]benzoic acid (1) as well as eleven known compounds were isolated from the fermentation product of the strain FS508. Their structures were determined by NMR, IR, UV, and MS spectroscopic data analyses. All the isolated compounds were evaluated for cytotoxic and anti-inflammatory activities. Among them, compounds 3 and 9 displayed potent cytotoxicity against HepG-2 cell line, and compounds 2, 3 and 12 showed significant anti-inflammatory activities.

Cytotoxic pyrone derivatives from the deep-sea-derived fungus Cladosporium halotolerans FS702.

Two new compounds (R)-6-((8S)-hydroxypropyl)-2-methyl-5,6-dihydro-4H-pyran-4-one (1) and (R)-6-((8R)-hydroxypropyl)-2-methyl-5,6-dihydro-4H-pyran-4-one (2), together with four known compounds were isolated from the marine-derived fungus Cladosporium halotolerans FS702. The structures of these compounds were determined on the basis of extensive spectroscopic analysis including 1D/2D NMR, IR, UV, HRESIMS, ECD calculations as well as the modified Mosher's method. Cytotoxic assay results showed that compound 2 had significant cytotoxic activity against SF-268, MCF-7, HepG-2, and A549 cells lines with IC50 values of 0.16, 0.47, 0.33 and 0.23 µM, respectively.

3-Carboxy-indole derivatives from the deep-sea-derived fungus Phomopsis tersa FS441.

Three new compounds phomtersines A-C (1-3) together with nine known compounds were isolated from the marine-derived fungus Phomopsis tersa FS441. Their structures were sufficiently established by spectroscopic methods, including extensive 1D and 2D NMR techniques and modified Snatzke's method. Moreover, compounds 1-12 were evaluated for cytotoxic and anti-inflammatory activities. As a result, phomtersine B (2) and the known compound 10 showed moderate cytotoxic activity against the four tested cell lines with IC50 values ranging from 20.21 to 36.53 µM, and phomtersine A (1) exhibited moderate inhibitory activity against LPS-induced NO production.

Cytospotones A-D, four new polyketones from the endophytic fungus Cytospora sp. A879.

Three new α-pyrone derivatives cytospotones A-C (1-3) and a new cyclohexenone derivative cytospotone D (4) together with four known α-pyrones were isolated from the endophytic fungus Cytospora sp. A879 of Pogostemon cablin (Blanco) Benth. The structures of 1-4 were elucidated primarily by spectroscopic methods (1D, 2D NMR and HRESIMS), ECD spectra analyses, and ECD calculations. Furthermore, the four new compounds (1-4) were evaluated for their anti-inflammatory and α-glucosidase inhibitory activities. The results showed that compound 1 had moderate inhibitory effect on LPS-induced NO production in RAW 264.7 macrophages.

A novel electro-Fenton hybrid system for enhancing the interception of volatile organic compounds in membrane distillation desalination.

Membrane distillation (MD) is a promising alternative desalination technology, but the hydrophobic membrane cannot intercept volatile organic compounds (VOCs), resulting in aggravation in the quality of permeate. In term of this, electro-Fenton (EF) was coupled with sweeping gas membrane distillation (SGMD) in a more efficient way to construct an advanced oxidation barrier at the gas-liquid interface, so that the VOCs could be trapped in this layer to guarantee the water quality of the distillate. During the so-called EF-MD process, an interfacial interception barrier containing hydroxyl radical formed on the hydrophobic membrane surface. It contributed to the high phenol rejection of 90.2% with the permeate phenol concentration lower than 1.50 mg/L. Effective interceptions can be achieved in a wide temperature range, even though the permeate flux of phenol was also intensified. The EF-MD system was robust to high salinity and could electrochemically regenerate ferrous ions, which endowed the long-term stability of the system. This novel EF-MD configuration proposed a valuable strategy to intercept VOCs in MD and will broaden the application of MD in hypersaline wastewater treatment.

Isolation and functional identification of immune cells in hemolymph of blood clams Tegillarca granosa.

Blood clam Tegillarca granosa is a type of economically cultivated bivalve mollusk with red blood, and it primarily relies on hemocytes in its hemolymph for immune defense. However, there are currently no reports on the isolation and identification of immune cells in T. granosa, which hinders our understanding of their immune defense. In this study, we employed single-cell transcriptome sequencing (scRNA-seq) to visualize the molecular profile of hemocytes in T. granosa. Based on differential expression of immune genes and hemoglobin genes, hemocytes can be molecularly classified into immune cells and erythrocytes. In addition, we separated immune cells using density gradient centrifugation and demonstrated their stronger phagocytic capacity compared to erythrocytes, as well as higher levels of ROS and NO. In summary, our experiments involved the isolation and functional identification of immune cells in hemolymph of T. granosa. This study will provide valuable insights into the innate immune system of red-blood mollusks and further deepen the immunological research of mollusks.

MiR- 211 represses apoptosis of nerve cells in rats with cerebral infarction through PI3K/AKT signaling pathway.

To investigate the effect of micro ribonucleic acid (miR)-211 on the apoptosis of nerve cells in rats with cerebral infarction through phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. A total of 36 Sprague-Dawley (SD) rats were randomly divided into sham operation group (n=12), model group (n=12) and miR-211 mimics group (n=12). Only the common carotid artery, external carotid artery, and internal carotid artery were exposed in sham operation group, and the models of cerebral infarction were constructed via suture method in the other two groups. After modeling, the rats in sham operation group and model group were intraperitoneally injected with normal saline, while those in miR-211 mimics group were given miR-211 mimics via intraperitoneal injection. At 2 weeks after intervention, samples were collected. Neurological deficit in rats was assessed using the Zea-longa score, and Nissl staining assay was performed to observe neuronal morphology. Western blotting (WB), quantitative polymerase chain reaction (qPCR) assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure the relative protein expressions of PI3K and phosphorylated AKT (p-AKT), mRNA expression of miR-211 and content of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), respectively. Additionally, the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. The neuronal morphology was normal in sham operation group, while it was disordered in model group, with damaged neurons. In miR-211 mimics group, the morphology of neurons was improved. The Zea-longa score was obviously higher in model group and miR-211 mimics group than that in sham operation group (P<0.05), while it was notably lower in miR-211 mimics group than that in model group (P<0.05). Compared with those in sham operation group, the relative protein expression levels of PI3K and p-AKT remarkably declined in model group and miR-211 mimics group (P<0.05), whereas they were clearly higher in miR-211 mimics group than those in model group (P<0.05). The relative expression level of miR-211 was lower in model group and miR-211 mimics group than that in sham operation group (P<0.05), while it was markedly higher in miR-211 mimics group than that in model group (P<0.05). In comparison with sham operation group, model group and miR-211 mimics group had remarkably increased content of Bax and evidently lowered content of Bcl-2 (P<0.05), whereas compared with model group, miR-211 mimics group displayed clearly reduced Bax content and notably raised Bcl-2 content (P<0.05). The apoptosis rate was distinctly higher in model group and miR-211 mimics group than that in sham operation group (P<0.05), while it was visibly lower in miR-211 mimics group than that in model group (P<0.05). MiR-211 represses the apoptosis of nerve cells in rats with cerebral infarction by up-regulating the PI3K/AKT signaling pathway, thereby protecting nerves.

Simultaneous Desalination and Glyphosate Degradation by a Novel Electro-Fenton Membrane Distillation Process.

The industrial effluent from glyphosate production has high salinity and refractory organic contaminants. The removal of organics and the recycling of inorganic salts from this kind of water are challenging issues. In this study, electro-Fenton (EF) and membrane distillation (MD) were coupled in a single reactor utilizing a membrane-based electrode (Mem-GDE) with the ability to bidirectionally transfer vapor and oxygen and electrochemically synthesize H2O2. The operating thermal conditions for MD significantly promoted Fenton reactions and, thus, the removal of glyphosate. During operation, Fe species deposited on the Mem-GDE and enhanced its catalytic activity and adsorptive capacity, which markedly increased the apparent reaction rate constant of glyphosate by 6 times. This novel EF-MD process simultaneously removed organics and concentrated the inorganics, which is very meaningful for decreasing the costs for subsequent crystallization and achieving high-quality crystal salts. This study provides an efficient method for the treatment of organic-inorganic hybrid wastewater.

Recent advances in radical-mediated intermolecular (4 + 2) cycloaddition.

(4 + 2) Cycloaddition plays an important role in the synthesis of versatile carbocyclic/heterocyclic compounds with its high atom- and step-economy. Additionally, with mild conditions and indispensable functional group compatibility, the radical reaction has been recognized as a useful tool in organic chemistry. Given the enormous impact of radical-mediated (4 + 2) cycloaddition processes and their promising applications, we summarize and highlight the recent works in this attractive area. On the basis of the types of radicals that initiate different (4 + 2) cycloaddition processes, we classify them into processes involving alkenyl cations or alkenyl radicals, aryl radicals, acyl radicals, alkyl radicals, and heteroatom radicals, and this review places special emphasis on the reaction design and mechanisms, which will stimulate future developments in radical-mediated intermolecular (4 + 2) cycloaddition.

[Effects of Yizhi Tiaoshen acupuncture on learning and memory function and the expression of phosphorylated tau protein in the hippocampus of Alzheimer's disease model rats].

OBJECTIVE: To observe the effects of Yizhi Tiaoshen (benefiting mental health and regulating the spirit) acupuncture on learning and memory function, and the expression of phosphorylated tubulin-associated unit (tau) protein in the hippocampus of Alzheimer's disease (AD) model rats, and explore the effect mechanism of this therapy on AD. METHODS: A blank group and a sham-operation group were randomly selected from 60 male SD rats, 10 rats in each one. AD models were established in the rest 40 rats by the intraperitoneal injection of D-galactose and okadaic acid in the CA1 region of the bilateral hippocampus. Thirty successfully-replicated model rats were randomly divided into a model group, a western medication group and an acupuncture group, 10 rats in each one. In the acupuncture group, acupuncture was applied to "Baihui" (GV 20), "Sishencong" (EX-HN 1), "Neiguan" (PC 6), "Shenmen" (HT 7), "Xuanzhong" (GB 39) and "Sanyinjiao" (SP 6); and the needles were retained for 10 min. Acupuncture was given once daily. One course of treatment was composed of 6 days, with the interval of 1 day; the completion of treatment included 4 courses. In the western medication group, donepezil hydrochloride solution (0.45 mg/kg) was administrated intragastrically, once daily; it took 7 days to accomplish one course of treatment and a completion of intervention was composed of 4 courses. Morris water maze (MWM) and novel object recognition test (NORT) were used to assess the learning and memory function of the rats. Using HE staining and Nissl staining, the morphological structure of the hippocampus was observed. With Western blot adopted, the protein expression of the tau, phosphorylated tau protein at Ser198 (p-tau Ser198), protein phosphatase 2A (PP2A) and glycogen synthase kinase-3ß (GSK-3ß) in the hippocampus was detected. RESULTS: There were no statistical differences in all of the indexes between the sham-operation group and the blank group. Compared with the sham-operation group, in the model group, the MWM escape latency was prolonged (P<0.05), the crossing frequency and the quadrant stay time in original platform were shortened (P<0.05), and the NORT discrimination index (DI) was reduced (P<0.05); the hippocampal cell numbers were declined and the cells arranged irregularly, the hippocampal neuronal structure was abnormal and the numbers of Nissl bodies decreased; the protein expression of p-tau Ser198 and GSK-3ßwas increased (P<0.05) and that of PP2A decreased (P<0.05). When compared with the model group, in the western medication group and the acupuncture group, the MWM escape latency was shortened (P<0.05), the crossing frequency and the quadrant stay time in original platform were increased (P<0.05), and DI got higher (P<0.05); the hippocampal cell numbers were elevated and the cells arranged regularly, the damage of hippocampal neuronal structure was attenuated and the numbers of Nissl bodies were increased; the protein expression of p-tau Ser198 and GSK-3ß was reduced (P<0.05) and that of PP2A was increased (P<0.05). There were no statistically significant differences in the above indexes between the acupuncture group and the western medication group (P>0.05). CONCLUSION: Acupuncture therapy of "benefiting mental health and regulating the spirit" could improve the learning and memory function and alleviate neuronal injure of AD model rats. The effect mechanism of this therapy may be related to the down-regulation of GSK-3ß and the up-regulation of PP2A in the hippocampus, and then to inducing the inhibition of tau protein phosphorylation.

Photoredox and Copper Dual-Catalyzed Cyclization of Alkyne-tethered α-Bromocarbonyls.

The synergistic systems of photoredox and copper catalyst have already appeared as a novel formation of green synthetic chemistry, which open new avenues for chemical synthesis applications. We describe a novel strategy for the cyclization of alkyne-tethered α-bromocarbonyls initiated by the cleavage of C(sp3 )-Br bond via the collaboration of photoredox and copper catalyst. The present protocol exhibits mildness using economical copper catalyst and visible-light at room temperature. The gram-scale and sunlight irradiation experiments proceeded smoothly to show the practicality of the methodology. It is notable that the newly generated oxygen in the product originates from H2 O.